DESCRIPTION The understanding of how a cell responds to mechanical stimulation from the environment is poorly developed. The cytoskeleton and adhesion molecules are important for these responses yet their roles remain ill defined. Mechanical input can affect gene expression, apoptosis, cell growth and cell motility, processes that are crucial for normal cellular function. In this proposal, we will investigate the role of mechanical stimuli during the actin-based process of phagocytosis, a previously unexplored area in terms of mechanosensing. Using a technique developed in our lab for the detection of mechanical response, we will investigate how Fc receptor-mediated phagocytosis is affected by mechanosensing and whether it can discriminate between rigid and soft materials. With the use of inhibitors and stimulators we will define the mechanosensitive pathways responsible for the cytoskeletal response. In addition, we will calculate and map the organization of the forces exerted during phagocytosis, which will bring further insight into how mechanical forces are involved in the engulfment process. Finally we will compare the mechanical behaviors of complement and Fc-mediated phagocytosis to determine how and why these mechanisms are so different. These studies will contribute to the understanding of how phagocytosis, a critical immunological process, is initiated.